Ebola virus glycoprotein demonstrates differential cellular localization in infected cell types of nonhuman primates and guinea pigs

Background.-In vitro studies have previously shown that Ebola virus glycopr otein (CP) is rapidly processed and largely released from infected cells, w hereas other viral proteins, such as VP40, accumulate within cells. Objective.-To determine infected cell types in which Ebola virus GP and VP4 0, individually, localize in vivo. Methods.-Immunohistochemistry and in situ hybridization using GP- and VP40- specific antibodies and genetic probes were used to analyze archived tissue s of experimentally infected nonhuman primates and guinea pigs and Vero E6 and 293 cells infected in vitro. Results.-The GP antigen was consistently present in hepatocytes, adrenal co rtical cells, fibroblasts, fibroblastic reticular cells, ovarian thecal cel ls, and several types of epithelial cells, but was not detected in macropha ges and blood monocytes of animals, nor in Vero cells and 293 cells. All GP -positive and CP-negative cell types analyzed contained VP40 antigen and bo th GP and VP40 RNAs. Conclusions.-Ebola virus GP appears to selectively accumulate in many cell types infected in vivo, but not in macrophages and monocytes. This finding suggests that many cell types may have a GP-processing pathway that differs from the pathway described by previous in vitro studies. Differential cell ular localization of CP could be relevant to the pathogenesis of Ebola hemo rrhagic fever.